This proposal seeks to determine whether the competence of vector ticks as hosts for Lyme disease spirochetes may be modified by the immune response of vertebrate hosts, thereby linking reservoir and vector competence. Using the uniquely competent white-footed mouse as a model, a sequence of experiments determine whether particular borrelial antigens such as OspA or OspB may induce humoral or cell-mediated immune responses that serve to negate spirochetal development within the guts of subadult deer ticks. In addition the hypothesis that anti-Osp mediated selection within the guts of ticks may contribute to spirochetal antigenic heterogeneity shall be explored, thereby demonstrating that the pathogen actively coevolves with the vector and reservoir. Finally, other spirochetal antigens shall be examined for their capacity to induce reservoir immune responses which may reduce or enhance vector competence by virtue of effects within the gut of the tick vector. Ultimately, this research effort is designed to define a physiological determinant of reservoir and vector competence for the agent of Lyme disease. It is anticipated-that these observations on the manner in which a pathogen interacts with its reservoir and vector may provide basic information on the mode of perpetuation of tick-borne microorganisms in nature.